Institut Imagine, INSERM U1163 - CNRS ERL8254, Paris, France.
Institut Imagine, INSERM U1163 - CNRS ERL8254, Paris, France; Département d'hématologie, Institut Gustave Roussy, Villejuif, France.
Pharmacol Res. 2019 Feb;140:67-74. doi: 10.1016/j.phrs.2018.08.005. Epub 2018 Aug 11.
A large number of studies have focused on the role of serotonin as a neurotransmitter in the central nervous system, although only a small percentage of the body's serotonin (∼5%) can be found in the mature brain of mammals. In the gut, the enterochromaffin cells are scattered in the enteric epithelium from the stomach through the colon and produce over 95% of the body's serotonin. Since the generation of tryptophan hydroxylase (Tph1 and Tph2) knockout mice, unsuspected roles have been identified for serotonin synthesized outside the brain. Moreover, the murine model deficient in peripheral serotonin (Tph1) is a unique experimental tool for exploring the molecular and cellular mechanisms involving serotonin's local effects through microserotonergic systems. In this review, we focus on peripheral serotonin and its role on progenitor or stem cells as well as on hematopoietic progenitors. We discuss the possible role of serotonin in hematopoietic diseases, and whether targeting the serotonergic system could be of therapeutic value for the regulation of normal and pathological hematopoiesis.
大量研究集中于血清素作为中枢神经系统神经递质的作用,尽管哺乳动物成熟脑中的血清素只有约 5%来源于身体。在肠道中,肠嗜铬细胞分散在肠上皮中,从胃到结肠都有分布,产生了超过 95%的身体血清素。自从色氨酸羟化酶(Tph1 和 Tph2)基因敲除小鼠出现以来,人们发现了大脑外合成的血清素的意想不到的作用。此外,缺乏外周血清素(Tph1)的小鼠模型是一种独特的实验工具,可用于通过微血清素能系统探索涉及血清素局部作用的分子和细胞机制。在这篇综述中,我们重点关注外周血清素及其在祖细胞或干细胞以及造血祖细胞上的作用。我们讨论了血清素在造血疾病中的可能作用,以及针对血清素能系统是否可能对调节正常和病理造血具有治疗价值。